TarGeting B-Cell Diseases

Jefferies London Healthcare Conference

November 2019

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This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements are often, but not always, made through the use of words or phrases such as “anticipates”, “expects”, “plans”, “believes”, “intends”, and similar words or phrases. Such statements involve risks and uncertainties that could cause TG Therapeutics’ actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks and uncertainties inherent in clinical trials, drug development, and commercialization. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and TG Therapeutics undertakes no obligation to update these statements, except as required by law.

Forward Looking Safe Harbor Statement

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TG is a biotechnology company focused on developing

medicines for patients with B-cell diseases:

• Chronic Lymphocytic Leukemia

• Marginal Zone Lymphoma

• Follicular Lymphoma

• Diffuse Large B-Cell Lymphoma

• Multiple Sclerosis

• Myasthenia Gravis

• Rheumatoid Arthritis

• Lupus

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Unique Approach to Drug Development

IDENTIFY ACQUIRE DEVELOP

Identify validated targets for B-cell

diseases

• Based on preclinical or clinical data known to be important in the treatment of B-cell disease

Search & Acquire “Best-in-Class”

Compounds

• Compounds that have the potential to offer improvements over available therapies

Develop Multi-drug Combinations

• To develop functional cures for cancers requires multiple drugs…solutions development

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B-Cell Focused PlatformClinical Stage Portfolio Overview

Product

Mechanism of

Action

Stage of

Development

Umbralisib (TGR-1202) PI3Kδ/CK1ε Phase 3

Ublituximab(TG-1101) Anti-CD20 Phase 3

TG-1501 Anti-PD-L1 Phase 1b

TG-1701 BTKi Phase 1

TG-1801 Anti-CD47/CD19 Phase 1

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Marginal Zone Lymphoma YE 2019

Umbralisib: Investigational Targeted Therapy with “Best-in-Class” Potential

LATE CLINICAL

DEVELOPMENT

US REGULATORY

SUBMISSION PLAN

CLL (in combo with Ublituximab) 1H2020

Follicular Lymphoma 2020

Small Lymphocytic Lymphoma 2020

Umbralisib

Next Generation PI3K delta inhibitor

Overcomes 1st generation Toxicity

Activity across NHL and CLL

Once daily oral dosing vs. BID or IV

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First Generation PI3K-delta’s are highly active but tolerability has limited market utilization

(1) Zydelig full-prescribing information; (2) Copiktra full-prescribing information; (3) Aliqopa full-prescribing information

• Fatal and/or serious hepatotoxicity occurred in 16% -18% of Zydelig-treated patients

• Fatal and/or serious diarrhea or colitis occurred in 14% - 20% of Zydelig-treated patients

• Fatal and/or serious pneumonitis occurred in 4% of Zydelig-treated patients

• Fatal and/or serious infections occurred in 21% - 48% of patients treated with Zydelig monotherapy

• Fatal and/or serious infections occurred in 31% of Copiktra-treated patients

• Fatal and/or serious diarrhea or colitis occurred in 18% of Copiktra-treated patients

• Fatal and/or serious cutaneous reactions occurred in 5% of Copiktra-treated patients

• Fatal and/or serious pneumonitis occurred in 5% of Copiktra-treated patients

• Infections: Serious, including fatal, infections occurred in 19% of Aliqopa-treated patients

• Hyperglycemia: Grade 3 or 4 hyperglycemia occurred in 41% of Aliqopa-treated patients

• Hypertension: Grade 3 hypertension occurred in 26% of Aliqopa-treated patients

• Non-Infection Pneumonitis:Occurred in 5% of Aliqopa-treated patients

• Severe Cutaneous Reactions:Grade 3 and 4 cutaneous reactions occurred in 2.8% and 0.6% of Aliqopa-treated patients, respectively

Black-Box Warning(1) Black-Box Warning(2) Warnings and Precautions(3)

Market is in need of a well tolerated PI3K-delta

DuvelisibIdelalisib Copanlisib

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Umbralisib: Selectivity

Umbralisib

DiscoverX KINOMEscan

Burris, et al., Lancet Oncology 2018

Umbralisib exhibits greater selectivity to PI3k-delta compared to other PI3K

inhibitors

Red circles indicate which kinase is being inhibited

The larger the red circle, the stronger the relative inhibition of the kinase

Delta

In-vitro kinase profiling – all compounds at 1µM

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Umbralisib: Selectivity

CK1e

DiscoverX KINOMEscan

Burris et al., Lancetr Oncology 2018; Maharaj et al., ASH 2017

PI3K associated immune-

mediated toxicities are thought

to be related to impaired Tregs

(Lampson et al., Blood 2016)

Umbraliib uniquely inhibits

CK1-epsilon, an important

conduit which may play a role

in Treg development and

function

Combination of CK1-epsilon

targeting and lack of inhibition

of PI3K gamma may prevent

impairment of Tregs, explaining

the improved tolerability profile

observed for umbralisib.

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Discontinuations

due to AEs were

rare at under 10%

Davids et al, EHA 2018

Integrated Safety Analysis of Umbralisib (n=347)

Umbralisib: Tolerability

All Grades, All Causality, AEsOccurring in >15% of Patients

Diarrhea 44%

Nausea 39%

Fatigue 35%

Neutropenia 22%

Anemia 20%

Vomiting 19%

Dizziness 18%

Thrombocytopenia 18%

Cough 17%

Decreased appetite 16%

Headache 16%

Neutropenia 16%

Anemia 5%

Thrombocytopenia 5%

Diarrhea 4%

Pneumonia 4%

Dyspnea 3%

Hypokalemia 3%

Grade 3/4, All Causality, AEs Occurring in >2% of Patients

Immune-mediated adverse events were infrequent: transaminitis (9%; Gr.3/4 2%); colitis (<1.5%; Gr.3/4 <1%); pneumonitis (<1.5%; Gr.3/4 <0.5%)

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CLL FL MZL

Umbralisib Single Agent Phase 1 Results (as published in Lancet Oncology)

Umbralisib: Activity

Lancet Oncology, February 2018

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Data Supporting Planned Umbralisib Filing In MZLBreakthrough Therapy Designation Granted

Fowler N, et. al., ASCO 2019

MZL Preliminary Safety & Tolerability

Umbralisib was deemed to be well tolerated

No events of colitis reported

AE’s leading to dose reduction occurred in 6 subjects (9%)

10 subjects (14%) discontinued umbralisib due to an AE considered at least possibly related to treatment

No deaths occurred on study

Grade 3 infections were limited, occurring in 3 patients (bronchitis, pneumonia, and influenza)

MZL Trial met primary endpoint exceeding target 40% ORR

Following Discussions with FDA Plan to Commence Rolling

Submission around YE2019

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MZL patients have few treatment options and no available cures

Approximately 7,500 new cases per year, with ~3,000 relapsed

patients needing treatment each year

Second largest indolent form of NHL

Affects mostly elderly individuals

Need for highly active, well-tolerated treatment option for MZL

Umbralisib: Convenient oral daily dosing appears well tolerated with

~50% ORR in MZL

Chemo-immunotherapy: non-specific, toxic contraindicated

in certain unfit elderly patients

R2: recently approved Revlimid plus Rituxan– can cause

severe neutropenia and rash; secondary malignancy risks

Ibrutinib: accelerated approval – less than half of patients

respond; tolerability issues

PI3K Delta inhibitors: none approved

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UNITY-NHL Umbralisib Monotherapy CohortFollicular Lymphoma (FL)

UNITY-NHL TrialFL Cohort

Fully Enrolled

Umbralisib

(TGR-1202)

Monotherapy

Follicular Cohort Met Primary End Point

Exceeding 40% ORR hurdle

Umbralisib monotherapy appeared to be

well tolerated with a safety profile

consistent with previous reports

TG plans to discuss the results with the

FDA to determine submission opportunities

for accelerated approval in FL

Other PI3K delta’s obtained accelerated

approved (range: 42% - 59% ORR)

Approximately 15,000 new FL cases per year

with ~7,500 relapsed patients needing

treatment per year

Full Enrollment

Complete

Target ORR 40-50%

Enrollment Complete 3Q-18

Target Full Data

Presentation

2020

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Relapsed/Refractory Indolent Commercial Opportunity

Sources: (1) Lymphoma Research Foundation; (2) Putnam Associates, 2018; (3) Thieblemont C., et al. Blood 2016; (4) TG Therapeutics AACR 2019

Market Overview

Two largest group of indolent lymphomas

(FL & MZL)1

~6,000-10,000 Patients inR/R Setting2

Median age at diagnosis is 60 years.1

Vast majority of patients will experience a relapse.3

Safe

ty

Umbralisib(MZL)

Once-daily, oral, non-chemotherapy treatment that is well tolerated and

efficacious4

CR = ~20%

No colitis

ORR = ~50%

Current Landscape

For a patient population that will ultimately experience multiple

lines of therapy, current options represent suboptimal tradeoff

between efficacy and safety

Efficacy

BTK

CD20 Regimens

Umbra &U2

PI3K Delta’s

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Multiple Sclerosis YE 2020

Ublituximab: Investigational Next Generation Anti-CD20 Monoclonal Antibody

LATE CLINICAL

DEVELOPMENT

US REGULATORY

SUBMISSION PLAN

CLL (in combo with umbralisib) 1H 2020

Ublituximab

Glycoengineered for enhanced potency over 1st generation

Activity in Rituxan refractory patients

Shorter infusions than all other anti-CD20s (1-1.5 v 3-4 hours)

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Early Clinical Data for Umbralisib and U2 in CLL Support Successful Phase 3

Study Enrollment ~420

Primary Endpoint PFS

Target PFS Readout 2H-19/1H-20

Patient Population 1L/2L+

Conducted under Special Protocol

Assessment

Progression-Free Survival

(Published in

Lancet Oncology

February 2018)

85% ORRUmbralisib

monotherapy

(at higher doses)

Median PFS for Umbralisib Monotherapy: 24 Months

Mato A, et. al, EHA 2016

Median PFS and DORnot reached for U2

U2 Umbralisib

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CLL is One of the Fastest Growing Global Hematology Markets

~115,000 Americans living with CLL

~20,000 newly-diagnosed patients each year

~20,000 previously treated patients seeking treatment each year

*Evaluate Pharma

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Chemo-immunotherapy: non-

specific, toxic contraindicated in

certain unfit elderly patients

BTK inhibitors: tolerability issues can

be significant

PI3K delta inhibitors: tolerability

prevents widespread utilization;

idelalisib contraindicated in first line

therapy

BCL2 inhibitors: potential for severe

tumor lysis syndrome requires

enhanced monitoring and

hospitalization in many cases

Need for additional highly active, well-tolerated

treatments for CLL

CLL remains incurable despite new treatment options

50,000+ patients treated in the US

135,000 patients treated WW

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U2 Offers a Needed Novel Treatment Option for CLLAlternative to or Complementary with Standard of Care

This slide represents the landscape from the Company’s perspective. Actual results may differ materially from those assumed by the Company and should not be relied upon for any purpose.

~36,000 CLL Patients Initiate a New Line of Therapy Annually in the US

BTK Experienced

BTK Naïve

Community Practices85%

Academic Practices15%

In poor candidates for BTK

+ BTK to enhance efficacy

In patients

rel/ref/intolerant to BTK

In patients rel/ref/intolerant

to BTK

+ Ven with curative intent

*Venetoclax currently has limited utilization in the

community due to monitoring/safety challenges

In poor candidates for

BTK/Ven

+ Ven with curative intent

+ BTK to enhance efficacy

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B-Cell Platform Provides Next Gen Combo’s

Nastoupil et al, Lugano 2017

Mato, et al. ASH 2018

U2+Venetoclax:

• Rel/Ref CLL

• 100% PB MRD-

• Best reported to date

U2+TG-1701:

• Rel/Ref MZL/FL

• 100% ORR at lowest

dose tested of 1701

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Ublituximab in Multiple Sclerosis

~1M Americans living

with MS

Completed Phase 2

ECTRIMS 2019:

Final Phase 2

efficacy data &

long-term safety

data

First look at

ULTIMATE I & II

Phase 3 study

design & patient

demographic data

Fully Enrolled Phase 3 ULTIMATE Trials

under Special Protocol Assessment (SPA)

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MS – Phase 2 ARR Comparison

0.05

0.13

0.64

0.36

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

UblituximabWeek24Phase 2(n=48)

OcrelizumabWeek 24Phase 2(n=55)

PlaceboWeek 24Phase 2(n=54)

Rebif(interferon beta-1a)

Phase 2(n=54)

Annualized Relapse Rate (ARR) Comparator

Final Ublituximab Phase 2 Data at Week 48

48 patients through 48 weeks of treatment

Annualized Relapse Rate of .07

Fox et. al., ECTRIMS October 2018

Kappos L et al. Lancet. 2011; 378:1779-1787

Hauser SL et al. NEJM. 2017; 376:221-234

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Ublituximab Phase 2: MRI-Gd Enhancing Lesions

Fox E et al., ECTRIMS 2018

No T1 Gd-enhancing

lesions were detected in

any subjects at Week 24 or

Week 48

(100% reduction; p=0.003)

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Significant Opportunity for Ublituximab in MS

Global Prevalence = ~2.3Million

Global Market Size >$30Billion by 2025

Source: Datamonitor 2018 MS Report

Prevalence Estimate: Nat’l MS Society

Roche JPM 2018 Corporate Update

0

5

10

15

20

25

30

35

2018 2019 2020 2021 2022 2023 2024 2025

$ B

illio

ns

Estimated Global Sales

US Ex-US (Japan, France, Germany, Italy, Spain & UK)

Current estimated ocrelizumab share: ~12% of total MS market

Ocrelizumab >$2 Billion in 2018 annual sales

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Source: Evaluate Pharma, Wall Street Research

Multiple Treatment Options Coexist & Account for Meaningful Market Share

Class Drug

U.S. Approval

Date Route of Administration Dosing Global 2018 Revenues by Drug/Class ($ in millions) Global Historical Revenues by Class

Betaseron 1993 Subcutaneously 1x / 2 days

Avonex 1996 Intramuscularly 1x / week

Rebif 2002 Subcutaneously 3x / week

Extavia 2009 Subcutaneously 1x / 2 days

Plegridy 2014 Subcutaneously 1x / 2 weeks

Tysabri 2004 Intravenously 1x / 4 weeks

Lemtrada 2014 Intravenously 3x / year

Gilenya 2010 Orally 1x / day

Aubagio 2012 Orally 1x / day

Tecfidera 2013 Orally 2x / day

Ocrevus 2017 Intravenously 2x / year

Ofatumumab 2020 Subcutaneously 1x / 4 weeks TBD

Ublituximab 2021 Intravenously 2x / year TBD

Interferons

IV Potent

Immunomodulators

T-Cell Targeted Orals

CD20s

$448

$162

$1,732

$1,915

$643

$475

$1,864

$4,274

$1,945

$3,380

$2,406

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Ublituximab Value Proposition in MS

Equal to better activity with comparable safety

Convenience of 1 hour infusion every 6 months v.

3-4 hours for Ocrelizumab

Strategically priced to optimize patient access

Estimate $1-2B annual market opportunity in

the US alone for ublituximab in MS

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Targeted Key Data & Potential Filings/Approvals

Clinical

Regulatory

2H2019 - 1H2020 2H2020

Top-Line

UNITY-FL

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Corporate & Financial

TGTX (NASDAQ)

$7.93 (close on 11/19/2019)

~$96M (proforma as of 9/30/19)

~103M (fully-diluted, as of 8/2/2019)

Key Financial Statistics

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Price:

Shares:

Cash:

NASDAQ: TGTX